宿主衍生生长因子驱动ERK酸化和MCL1表达,在转移性肺殖民期间促进骨髓瘤细胞存活
Camille A McAloney1,2, Rawan Makkawi3, Yogesh Budhathoki2,4
1Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA.
Cellular oncology (Dordrecht, Netherlands)
|September 7, 2023
概括
存活肺转移的瘤细胞依赖MAPK途径和MCL1进行生长. 通过化疗抑制MCL1,有效地预防和治疗小鼠骨髓瘤转移.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症转移研究 癌症转移研究
背景情况:
- 肺转移是骨髓瘤患者死亡的主要原因.
- 了解瘤细胞在传播后的生存机制对于开发有效的抗转移疗法至关重要.
研究的目的:
- 确定分子机制,使得肺部传播骨髓瘤细胞的存活.
- 发现促进瘤细胞殖民和转移的宿主衍生信号.
主要方法:
- 对来自小鼠肺转移的单细胞RNA测序数据的分析.
- 使用活细胞记者系统,免疫细胞化学和药物抑制的验证.
- 在体内研究采用转移性骨髓瘤的小鼠模型.
主要成果:
- 在早期和已确定的转移中观察到MAPK通路活性升高和MCL1 (抗亡基因) 表达.
- 宿主利基细胞提供增长因子,增强ERK酸化和瘤细胞中的MCL1表达.
- 在小鼠模型中,MCL1抑制,特别是与化疗相结合时,在预防殖民和消除已建立的转移方面表现出有效性.
结论:
- 宿主衍生生长因子激活MAPK通路,并在骨髓瘤中调节MCL1,促进转移性殖民.
- 骨髓瘤转移仍然依赖于MCL1,即使在较晚的阶段.
- 抑制MCL1在人类和狗患者骨髓瘤转移方面是一个有前途的治疗策略.
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